Down syndrome (DS) is the most common genetic cause of mental retardation, with an incidence of 1 in 733 live births. The paucity of clinical researchers trained in the subspecialty of Developmental-Behavioral Pediatrics has meant that topics critical to improving the lives of children with DS have not received sufficient attention. For example, nearly half of all children with DS are born with a congenital heart defect (CHD), the most common of which is an atrioventricular septal defect (AVSD). As these children (DS + AVSD) increasingly survive cardiac surgery, characterization of their early developmental trajectories is crucial for designing early interventions to maximize individual potential. As a Developmental-Behavioral Pediatrician committed to enhancing the quality of life for individuals with DS, my long-term goal for this research is to optimize the neurodevelopmental outcomes of children with DS + AVSD and, eventually, with other DS-associated medical conditions. My Research Application builds upon results from my KL2-supported Masters of Science in Clinical Research, which revealed global developmental deficits in DS + AVSD. My Career Development Plan combines didactic coursework, tutorials, and hands-on training in psychology and psychometrics, genetics, cardiology, biostatistics, and health organization management to support my Research Plan. My Research Aims are 1) to determine the early developmental trajectories of children with DS + AVSD compared to age-matched DS without CHD and 2) to identify patient-related and perioperative factors and 3) home environmental variables (socioeconomic, parental stress, parent-child interactions) that influence developmental outcomes in DS + AVSD. To accomplish these Aims, developmental trajectories will be measured at 3, 12, and 24 months of age. The research and clinical capabilities of the Emory Down Syndrome Center are cornerstones of my Research Plan. Our DS clinic serves individuals from birth through early childhood. Since 71% of new patients are under 6 months of age, we are well positioned to recruit newborns with DS, including those with AVSD. My Research Plan dovetails seamlessly into the research arm of the Center, with its infrastructure built on 18 years of population-based DS research. My research will provide important information and suggest potential interventions to improve the lives of children with DS.